Neuroprotective synergy of erythropoietin and insulin-like growth factors

Abstract

The present invention provides a method of providing acute neuroprotection by inducing the erythropoietin (EPO) signaling pathway in neuronal cells close to or subsequent to the time of excitatory insult; and inducing an insulin-like growth factor (IGF) signaling pathway in the neuronal cells close to or subsequent to the time of excitatory insult, thereby producing a synergistic acute neuroprotective effect in the neuronal cells. The invention also provides a method of preventing or reducing the severity of a neurologic condition in a subject by administering to the subject EPO or an active fragment or analog thereof at a dose of at most 2000 U / kg; and administering to the subject an IGF or an active fragment or analog thereof, thereby providing neuroprotection and preventing or reducing the severity of the neurologic condition. Such a method can be used to prevent or reduce the severity of, for example, Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, amyotrophic lateral sclerosis, multiple sclerosis, a movement disorder, HIV-associated dementia, HIV-associated neuropathy, neuropathic pain, migraine, glaucoma, drug addiction, drug withdrawal, drug dependency, depression or anxiety.

Description

[0001]This application claims benefit of the filing date of U.S. Provisional Application No. 60 / 388,058, filed Jun. 11, 2002, and of U.S. Provisional Application No. 60 / 458,145, filed Mar. 26, 2003, which are incorporated herein by reference.[0002]This application was made with government support under P01 HD29587, R01 NS43242 and NS43242 awarded by the National Institute of Health. The government has certain rights in the invention.FIELD OF THE INVENTION[0003]The invention relates to the prevention and treatment of acute and chronic neurodegenerative conditions, and to erythropoietin and insulin-like growth factors and analogs of these factors.BACKGROUND INFORMATION[0004]For a variety of serious neurodegenerative diseases, there exist no effective therapies or cures. For example, Parkinson's disease is a progressive and ultimately fatal neurodegenerative disorder characterized by loss of the pigmented dopaminergic neurons of the substantia nigra. The symptoms of Parkinson's disease...

AI Technical Summary

Benefits of technology

[0007]The present invention provides a method of providing acute neuroprotection by inducing the erythropoietin (EPO) pathway in neuronal cells close to or subsequent to the time of excitatory insult; and inducing an insulin-like growth factor (IGF) pathway in the neuronal cells close to or subsequent to the time of excitatory insult, thereby producing a synergistic acute neuroprotective effect in the neuronal cells.

[0008]The present invention further provides a method of providing acute neuroprotection by contacting neuronal cells with EPO or an active fragment or analog thereof close to or subsequent to the time of excitatory insult; and contacting the neuronal cells with an IGF or an active fragment or analog thereof close to or subsequent to the time of excitatory insult, thereby producing a synergistic acute neuroprotective effect in the neuronal cells.

[0014]Also provided herein is a method of preventing or reducing the severity of an acute neurologic condition in a subject by administering to the subject EPO or an active fragment or analog thereof close to or subsequent to the time of acute injury; and administering to the subject an IGF or an active fragment or analog thereof close to or subsequent to the time of acute injury, thereby providing a synergistic acute neuroprotective effect and preventing or reducing the severity of the acute neurologic condition. Such an acute neurologic condition can be, without limitation, stroke, head or spinal cord trauma, or seizure.

[0025]The present invention also provides a method of preventing or reducing the severity of a cerebral neurologic condition in a subject by transnasally administering to the subject EPO or an active fragment or analog thereof at a dose of at most 2000 U / kg; and transnasally administering to the subject an IGF or an active fragment or analog thereof, thereby providing acute neuroprotection and preventing or reducing the severity of the neurologic condition.

Problems solved by technology

For a variety of serious neurodegenerative diseases, there exist no effective therapies or cures.

However, reduced efficacy of L-DOPA treatment typically occurs over time.

In Alzheimer's disease, the most common neurodegenerative disease and most frequent cause of dementia, progressive failure of memory and degeneration of temporal and parietal association cortex result in speech impairment and loss of coordination, and, in some cases, emotional disturbance.

Present therapies are relatively ineffective or are accompanied by unwanted side effects.

In particular, erythropoietin (EPO) can be neuroprotective when administered in high doses; however, such doses also promote the formation of new red blood cells, consequently causing side effects such as “sludging” of the blood and leading to increased risk of stroke.

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